ClinVar Miner

Submissions for variant NM_001242896.3(DEPDC5):c.1385A>G (p.Tyr462Cys)

gnomAD frequency: 0.00001  dbSNP: rs747546981
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002232302 SCV000642153 uncertain significance Familial focal epilepsy with variable foci 2024-12-24 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 462 of the DEPDC5 protein (p.Tyr462Cys). This variant is present in population databases (rs747546981, gnomAD 0.006%). This missense change has been observed in individual(s) with frontal lobe epilepsy (PMID: 30093711). ClinVar contains an entry for this variant (Variation ID: 466451). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
CeGaT Center for Human Genetics Tuebingen RCV001815403 SCV002064095 uncertain significance not provided 2021-11-01 criteria provided, single submitter clinical testing
GeneDx RCV001815403 SCV002586778 uncertain significance not provided 2024-09-05 criteria provided, single submitter clinical testing Reported previously in an individual with intellectual disability, seizures, and hemispheric malformation of cortical development; segregation information was not provided (PMID: 30093711); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 30093711)
Neuberg Centre For Genomic Medicine, NCGM RCV003338655 SCV004048396 uncertain significance Epilepsy, familial focal, with variable foci 1 criteria provided, single submitter clinical testing The missense variant c.1385A>G (p.Tyr462Cys) in DEPDC5 gene has been submitted to ClinVar as a Variant of Uncertain Significance. The c.1385A>G (p.Tyr462Cys) variant has not been reported in the literature in individuals with DEPDC5-related disease. The c.1385A>G (p.Tyr462Cys) variant is reported with the allele frequency (0.001%) in the gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. The amino acid Tyr at position 462 is changed to a Cys changing protein sequence and it might alter its composition and physico-chemical properties. The variant is predicted to be damaging by both SIFT and PolyPhen2. The residue is conserved across species. The amino acid change p.Tyr462Cys in DEPDC5 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Variant of Uncertain Significance (VUS).

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